rs1059828

Variant names:

• chr1-1707458-A-C
• rs1059828
• NM_024011.4:c.1196T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-1707458-A-C
• chr1-1707458-A-G
• chr1-1707458-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024011.4(CDK11A):​c.1196T>G​(p.Leu399Trp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000048 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDK11A NM_024011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41
• Publications: 9 publications found

Genes affected

CDK11A (HGNC:1730): (cyclin dependent kinase 11A) This gene encodes a member of the serine/threonine protein kinase family. Members of this kinase family are known to be essential for eukaryotic cell cycle control. Due to a segmental duplication, this gene shares very high sequence identity with a neighboring gene. These two genes are frequently deleted or altered in neuroblastoma. The protein kinase encoded by this gene can be cleaved by caspases and may play a role in cell apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ENSG00000268575 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14426997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	NM_024011.4	MANE Select	c.1196T>G	p.Leu399Trp	missense	Exon 11 of 20	NP_076916.2
	CDK11A	NM_001313896.2		c.1205T>G	p.Leu402Trp	missense	Exon 11 of 20	NP_001300825.1
	CDK11A	NM_001313982.2		c.1193T>G	p.Leu398Trp	missense	Exon 11 of 20	NP_001300911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	ENST00000404249.8	TSL:1 MANE Select	c.1196T>G	p.Leu399Trp	missense	Exon 11 of 20	ENSP00000384442.3
	CDK11A	ENST00000378633.5	TSL:1	c.1205T>G	p.Leu402Trp	missense	Exon 11 of 20	ENSP00000367900.1
	CDK11A	ENST00000357760.6	TSL:1	c.1193T>G	p.Leu398Trp	missense	Exon 11 of 20	ENSP00000350403.2

Frequencies

GnomAD3 genomes AF: 0.00000671 AC: 1 AN: 149134 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000819 AC: 2 AN: 244268 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000481 AC: 7 AN: 1456346 Hom.: 1 Cov.: 31 AF XY: 0.00000690 AC XY: 5 AN XY: 724422

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 85830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1107960

Other (OTH) AF: 0.00 AC: 0 AN: 60086

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000671 AC: 1 AN: 149134 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 72792

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39858

American (AMR) AF: 0.00 AC: 0 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67274

Other (OTH) AF: 0.00 AC: 0 AN: 2018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 4

ExAC AF: 0.0000663 AC: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	23
DANN	Benign	0.87
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.4
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.018	D
Polyphen		0.28	B
Vest4		0.41
MutPred		0.39		Loss of disorder (P = 0.031)
MVP		0.19
MPC		0.31
ClinPred		0.22	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.33
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1059828; hg19: chr1-1638897;